Chronic Pain
Conditions
Keywords
Virtual Reality, Web App, Digital Health, Rural
Brief summary
This study compared two available, evidence-based, at-home digital pain treatment programs. The goal is to see if one approach is better than the other, and whether certain patients respond to one more than the other. Study participants will be randomly assigned to receive one of two treatment programs: Skills-Based VR or painTRAINER. VR devices and painTRAINER manuals will be delivered to the participant's home with instructions for use via FedEx; participants will receive remote technical support. They will be followed for 12 weeks and complete Patient Reported Outcome (PRO) questionnaires to assess functional status, pain levels, and use of pain medications (including opioids). Participants will also be asked to provide consent/authorization to access medical records from their treating facility.
Detailed description
We performed a two-arm, multi-center, virtual randomized controlled trial (vRCT) in a geographically diverse group of patients with mixed-etiology chronic pain. Using a random number generator, patients were allocated in a 1:1 ratio between two self-administered, remotely deployed CBT delivery platforms, stratified by site: (1) a 2D mHealth app called PainTRAINER; and (2) 3D virtual reality (VR) app called EaseVRx+. The primary analysis compared changes in pain intensity over two months upon completion of the standardized 8-week digital CBT protocols. Secondary outcomes include pain catastrophizing, anxiety, pain interference, self-efficacy, and opioid use. Patient blinding is not possible in VR versus non-VR studies; however, researchers exhibited equipoise when describing the competing interventions, Investigators and data analysts were blinded to patient allocation; coordinators administering the intervention were unblinded in order onboard participants to their assigned program and troubleshoot any difficulties throughout the study. The population eligible for the study include individuals with any of more than 130 ICD codes for chronic pain conditions, including somatic, musculoskeletal, neuropathic, and visceral pain who also recorded an average pain intensity of 4 or greater on a standard 0-10 numeric rating scale (NRS) over the past week. Patients were recruited from three major sites: (1) Cedars-Sinai Health System (CSHS); (2) Ochsner Health; (3) UAB. All sites used search tools to identify participants within their respective electronic health record (EHR) with at least one of the inclusionary chronic pain ICD codes and who did not meet several coded ineligibility criteria, included but not limited to ongoing end-of-life care and an age less than 13 years old. Patients meeting preliminary eligibility were chart reviewed for confirmation, then contacted through methods approved by each respective site's IRB, which included combinations of email, physical mail, and patient-portal notifications. Patients were offered an opportunity to opt-in or opt-out, and those who do not respond were contacted by phone call to assess interest and eligibility. This trial was conducted remotely using patient identification, screening, and monitoring processes developed by the study team and applied in many trials involving virtual reality, including other NIH-sponsored trials using VR therapies for pain (NCT04409353, NCT04907643). Participants who provided eConsent and completed a 7-day "screener week" on REDCap were randomized and sent study materials by mail. Study onboarding was performed over the phone and did not require in-person interactions with the study team. We employed a biopsychosocial conceptual framework for monitoring outcomes in the trial, focusing on pain intensity as the primary outcome, and included a range of other relevant PROs selected in partnership with our patient partners. PROs were collected via REDCap. Pain intensity was measured using a standard 11-point numeric rating scale (NRS) with a 24-hour recall. Consistent with NIH Helping to End Addiction Long-Term (HEAL) guidance, we measured daily pain NRS for 7-days during baseline (week 0), and again during the final week of the digital program study (week 8). Intention-to-Treat (ITT) analysis of the primary endpoint involved comparing the proportion of individuals who recorded a minimally clinically importance difference (MCID) of two on the average pain NRS recorded between Week 8 and Week 0. Secondary outcomes include the 4-item short form pain catastrophizing scale, 4-item NIH PROMIS Anxiety scale, 4-item NIH PROMIS Pain Interference scale, 2-item Pain Self-Efficacy Questionnaire, and average opioid usage derived from total morphine milligram equivalents (MMEs) in self-reported medication use. In addition, VR presence and cybersickness at the start of intervention use using the Presence Scale and Simulator Sickness Questionnaire (SSQ), respectively.
Interventions
BEHAVIORALpainTRAINER®
PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events.
DEVICESkills-Based VR
Participants will use the Pico G2 4K VR audio and visual head-mounted device, loaded with the EaseVRx+ software. The Pico G2 4K is a standalone VR headset that comes with an orientation-tracked controller. It does not require a smartphone or personal computer to operate. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. The headset battery requires recharging after approximately 2.5 hours of use. https://www.pico-interactive.com/us/G2\_4K.html
Sponsors
Cedars-Sinai Medical Center
Northwestern University
Stanford University
University of Alabama at Birmingham
Ochsner Health System
National Institute of Nursing Research (NINR)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Masking description
Providers, Primary Investigator, and Biostatistician were all blinded to allocations until the end of data collection.
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
We will recruit patients who: (1) have chronic pain, from any underlying condition, using the administrative definition of ICD-10 code series G89.X or one or more of 134 chronic overlapping pain condition codes, as previously standardized and validated by an expert panel, (2) have experienced average pain intensity of \>3 out of 10 within the previous week, (3) are ≥13 years of age, (4) are able to read/write English, (5) have either a personal computer or a smartphone, and (6) live in a designated rural zip code as defined by the Federal Office of Rural Health Policy (FORHP) data (RUCA Codes 4-10). We will exclude patients who: (1) have a condition that interferes with use of the intervention (e.g., significant visual or auditory impairment, any history of seizure), (2) are hospitalized, (3) are receiving active cancer treatment, (4) are receiving end-of-life care, (5) have cognitive impairment that affects participation, or (6) have previously used the EaseVRx+ or painTRAINER programs. We will stratify analyses across key patient characteristics, including type of pain condition, sex, age, race, ethnicity, State and zip code, Rural-Urban Commuting Area (RUCA) codes (a composite measure of population density, urbanization, and daily commuting), pain severity, opioid use, comorbidities, social support, and COVID-19 impacts (unemployment, financial hardship, family or personal COVID-19 diagnosis).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Daily Pain Intensity | From baseline to end of treatment at Week 8 | \[Alternative Title: Proportion of Participants with \>=2 Change in Average of 7 Daily Pain Intensity Questionnaires\] The change from study baseline to week 8 in daily pain intensity was measured using the standard 11-point numeric rating scale (NRS) with a 24-hour recall. Daily pain NRS was measured for 7-days during baseline and again during the final week of the study (week 8). This outcome is the baseline vs. week 8 difference-in-difference in 7-day average NRS pain intensity scores, dichotomized into if the minimally clinically importance difference (MCID) of 2 is achieved. NRS is positively scored, where higher scores indicate worse pain intensity. The difference from baseline is reported as Baseline - Week 8, therefore a higher difference corresponds to improvement of symptoms (reduced pain intensity). The difference-in-difference is dichotomized into if the MCID of 2 is achieved, reported as the proportion of participants by arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient-Reported Outcomes Measurement Information System Pain Interference 4a (PROMIS-PI) T-score | From baseline to end of treatment at Week 8 | The Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) scale, version 4a, measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from "not at all" (1) to "very much" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced PI). |
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety T-score | From baseline to end of treatment at Week 8 | The Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale, version 4, assesses self-reported perceptions of fear, anxious misery (worry, dread), hyperarousal, and somatic symptoms related to arousal. Items are rated Items are rated on a 5-point Likert scale from "never" (1) to "always" (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-Anxiety is positively scored, where higher scores indicate worse anxiety. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced anxiety). |
| Change in 2-item Pain Self-Efficacy Questionnaire (PSEQ-2) | From baseline to end of treatment at Week 8 | The Pain Self-Efficacy Questionnaire (PSEQ-2) is a two-item instrument designed to assess the extent to which people in pain believe they are presently able to work and live a normal life, despite pain. "Work" includes housework and paid and unpaid work. Items are rated on a 7-point Likert scale from "not confident at all" (0) to "completely confident" (6), with a raw score calculated by a sum of the 2 items ranging from 0 to 12. PSEQ-2 is positively scored, where higher scores indicate greater self-efficacy. The difference from baseline is reported as Week 8 - Baseline, therefore a positive difference corresponds to improvement of symptoms (greater self-efficacy). |
| Change in 4-item Pain Catastrophizing Scale (briefPCS) | From baseline to end of treatment at Week 8 | Self-reported pain catastrophizing was measured using the 4-item Pain Catastrophizing Scale (briefPCS) questionnaire. Pain catastrophizing is a negative mental state regarding actual or anticipated pain, and includes aspects of rumination, magnification, and sense of helplessness. Pain catastrophizing is a highly potent prognostic indicator for acute analgesic use, and acute and chronic pain outcomes, yet is also highly modifiable with behavioral treatment that enhances pain self-regulation via evidence-based skills. Items are rated on a 5-point Likert scale from "not at all" (0) to "all the time" (4), with a raw score calculated by a sum of the 4 items, ranging from 0 to 16. briefPCS is positively scored, where higher scores indicate greater levels of pain catastrophizing. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain catastrophizing). |
| Change in Weekly Opioid Use (Use or No Use) | From baseline to end of treatment at Week 8 | Opioid medications are commonly prescribed for pain analgesia. Participants self-reported their prescription and over-the-counter pain medications, daily for 7 days, at baseline (days -6 to 0) and during Week 8 of the study (days 50-56). The questionnaire contains lists of opioids and non-opioids. Responses were categorized based on whether or not an individual reported the use of an opioid medication on at least one of the daily surveys during baseline and during week 8; responses are reported as the proportion of individuals who reported the use of an opioid and who completed at least 4 daily questionnaires during the specified time period, divided by the total number of individuals who completed at least 4 daily questionnaires during the time interval, by arm. A smaller proportion at week 8 corresponds to a decrease in the frequency of opioid use in the observed sample. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBrennan Spiegel, MD, MSHS
Cedars-Sinai Medical Center
Participant flow
Recruitment details
Participants were recruited from four clinical sites: Cedars-Sinai Medical Center (CA), Ochsner Health System (LA), University of Alabama at Birmingham (AL), and Bendcare (FL). Patient cohort search engines identified individuals with chronic pain, and their zip codes were matched with 2010 USDA RUCA data. Enrollment activities were conducted remotely, by telephone and electronic surveys. Recruitment spanned from 3/23/2022 to 2/27/2024 with final analyzable sample N=330 (N=300+30 replacements).
Pre-assignment details
Of 2,804 participants screened, 367 underwent the informed eConsent process and enrolled in the Screening Week. Of the 367 participants, 330 successfully met inclusion criteria and were randomized to one of two treatment arms.
Participants by arm
| Arm | Count |
|---|---|
| painTRAINER (2D mHealth Intervention) Participants will use one of the most widely-validated mHealth interventions for pain management called painTRAINER®, which is a standardized, 56-day program delivering skills training and Cognitive behavioral therapy (CBT)-related treatments through daily virtual experiences.
painTRAINER®: PainTRAINER is among the most widely-validated mHealth interventions for pain management.18-25 Originally developed by members of our team at Duke and Northwestern University under NIH funding, the app teaches evidence-based pain coping skills using a self-administered, home-based software program. The system delivers eight sessions via any web-connected platform, including Android or iOS smartphones, tablets, or personal computers. The digital curriculum covers progressive muscle relaxation, activity/rest cycling, pleasant activity scheduling, recognizing negative automatic thoughts, pleasant imagery/distraction, problem solving, and monitoring for maintenance. Patients complete one session per week in a pre-determined order. The program can be completed in a flexible manner to accommodate life and medical events. | 161 |
| Skills-based VR (3D VR Intervention) Participants will use a skills-based, self management VR program called EaseVRx+. Developed by AppliedVR (Los Angeles, CA) in partnership with Stanford pain psychologist Dr. Beth Darnall, the program teaches and trains users on evidence-based strategies and biofeedback exercises. EaseVRx+ combines psychoeducation, pain education, breathing training, relaxation exercises, and executive functioning games to provide a mind-body approach toward pain management. The standardized, reproducible, 56-day program delivers a combination of skills training and CBT-related treatments through scheduled daily virtual experiences. It also features an on-demand library, allowing users to access any of the unique video sessions as needed.VR experiences last between 2-16 minutes.
Participants will use the Pico G24K VR audio and visual head-mounted device, loaded with EaseVRx+. It does not require a smartphone or personal computer to operate and comes with an orientation-tracked controller. The device supports 3 degrees of freedom (3DOF) head tracking, has best-in-class optics, and a wide field-of-view. | 169 |
| Total | 330 |
Baseline characteristics
| Characteristic | Skills-based VR (3D VR Intervention) | Total | painTRAINER (2D mHealth Intervention) |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 12.9 | 54.9 years STANDARD_DEVIATION 12.5 | 54.4 years STANDARD_DEVIATION 12 |
| Education Associate's or Technical Degree Complete | 40 Participants | 78 Participants | 38 Participants |
| Education College or Baccalaureate Degree Complete | 25 Participants | 59 Participants | 34 Participants |
| Education Did not complete Secondary School or Less than High School | 2 Participants | 7 Participants | 5 Participants |
| Education Doctoral or Postgraduate Education | 14 Participants | 28 Participants | 14 Participants |
| Education High School or Secondary School Degree Complete | 65 Participants | 115 Participants | 50 Participants |
| Education Some Secondary School or High School Education | 23 Participants | 43 Participants | 20 Participants |
| Employment Full-time employment | 50 Participants | 101 Participants | 51 Participants |
| Employment Not employed | 102 Participants | 200 Participants | 98 Participants |
| Employment Part-time employment | 17 Participants | 29 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 24 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 156 Participants | 298 Participants | 142 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 5 Participants |
| Household Income $100,000-$149,999 | 13 Participants | 34 Participants | 21 Participants |
| Household Income $10,000-$24,999 | 30 Participants | 52 Participants | 22 Participants |
| Household Income $150,000-$199,999 | 7 Participants | 15 Participants | 8 Participants |
| Household Income $200,000 or more | 5 Participants | 9 Participants | 4 Participants |
| Household Income $25,000-$34,999 | 15 Participants | 33 Participants | 18 Participants |
| Household Income $35,000-$49,999 | 32 Participants | 52 Participants | 20 Participants |
| Household Income $50,000-$74,999 | 20 Participants | 44 Participants | 24 Participants |
| Household Income $75,000-$99,999 | 24 Participants | 43 Participants | 19 Participants |
| Household Income Less than $10,000 | 8 Participants | 21 Participants | 13 Participants |
| Household Income Prefer not to answer | 15 Participants | 27 Participants | 12 Participants |
| Participant Enrollment by Site Bendcare | 47 Participants | 93 Participants | 46 Participants |
| Participant Enrollment by Site Cedars-Sinai Health System | 33 Participants | 63 Participants | 30 Participants |
| Participant Enrollment by Site Ochsner Health | 56 Participants | 110 Participants | 54 Participants |
| Participant Enrollment by Site Other | 1 Participants | 3 Participants | 2 Participants |
| Participant Enrollment by Site University of Alabama at Birmingham (UAB) | 32 Participants | 61 Participants | 29 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 42 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 15 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 134 Participants | 263 Participants | 129 Participants |
| Sex: Female, Male Female | 122 Participants | 234 Participants | 112 Participants |
| Sex: Female, Male Male | 47 Participants | 96 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 161 | 0 / 169 |
| other Total, other adverse events | 13 / 161 | 47 / 169 |
| serious Total, serious adverse events | 3 / 161 | 4 / 169 |
Outcome results
Primary
Change From Baseline to Week 8 in Daily Pain Intensity
\[Alternative Title: Proportion of Participants with \>=2 Change in Average of 7 Daily Pain Intensity Questionnaires\] The change from study baseline to week 8 in daily pain intensity was measured using the standard 11-point numeric rating scale (NRS) with a 24-hour recall. Daily pain NRS was measured for 7-days during baseline and again during the final week of the study (week 8). This outcome is the baseline vs. week 8 difference-in-difference in 7-day average NRS pain intensity scores, dichotomized into if the minimally clinically importance difference (MCID) of 2 is achieved. NRS is positively scored, where higher scores indicate worse pain intensity. The difference from baseline is reported as Baseline - Week 8, therefore a higher difference corresponds to improvement of symptoms (reduced pain intensity). The difference-in-difference is dichotomized into if the MCID of 2 is achieved, reported as the proportion of participants by arm.
Time frame: From baseline to end of treatment at Week 8
Population: All analyses were performed by study arm using an Intent-to-treat (ITT) population defined as all randomized participants across each treatment arm. Participants that provided at least 4 out of 7 possibly daily responses at Week 8 were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| painTRAINER (2D mHealth Intervention) | Change From Baseline to Week 8 in Daily Pain Intensity | Difference is less than 2 | 85 Participants |
| painTRAINER (2D mHealth Intervention) | Change From Baseline to Week 8 in Daily Pain Intensity | Difference is greater than or equal to 2 | 40 Participants |
| Skills-based VR (3D VR Intervention) | Change From Baseline to Week 8 in Daily Pain Intensity | Difference is less than 2 | 118 Participants |
| Skills-based VR (3D VR Intervention) | Change From Baseline to Week 8 in Daily Pain Intensity | Difference is greater than or equal to 2 | 35 Participants |
Comparison: The primary outcome will be the baseline vs. week 8 difference-in-difference in 7-day average NRS pain intensity scores, dichotomized into if the MCID of 2 is achieved. The between arm difference of achieving the MCID of 2 will be tested using Chi-squared test.p-value: 0.088Chi-squared
Secondary
Change in 2-item Pain Self-Efficacy Questionnaire (PSEQ-2)
The Pain Self-Efficacy Questionnaire (PSEQ-2) is a two-item instrument designed to assess the extent to which people in pain believe they are presently able to work and live a normal life, despite pain. Work includes housework and paid and unpaid work. Items are rated on a 7-point Likert scale from not confident at all (0) to completely confident (6), with a raw score calculated by a sum of the 2 items ranging from 0 to 12. PSEQ-2 is positively scored, where higher scores indicate greater self-efficacy. The difference from baseline is reported as Week 8 - Baseline, therefore a positive difference corresponds to improvement of symptoms (greater self-efficacy).
Time frame: From baseline to end of treatment at Week 8
Population: All analyses were performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants. Participants that completed PSEQ-2 at Week 8 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| painTRAINER (2D mHealth Intervention) | Change in 2-item Pain Self-Efficacy Questionnaire (PSEQ-2) | 1.5 units on a scale | Standard Deviation 2.7 |
| Skills-based VR (3D VR Intervention) | Change in 2-item Pain Self-Efficacy Questionnaire (PSEQ-2) | 0.6 units on a scale | Standard Deviation 2.8 |
Comparison: A two-sample t-test will be used to compare differences-in-differences between the arms.p-value: 0.005t-test, 2 sided
Secondary
Change in 4-item Pain Catastrophizing Scale (briefPCS)
Self-reported pain catastrophizing was measured using the 4-item Pain Catastrophizing Scale (briefPCS) questionnaire. Pain catastrophizing is a negative mental state regarding actual or anticipated pain, and includes aspects of rumination, magnification, and sense of helplessness. Pain catastrophizing is a highly potent prognostic indicator for acute analgesic use, and acute and chronic pain outcomes, yet is also highly modifiable with behavioral treatment that enhances pain self-regulation via evidence-based skills. Items are rated on a 5-point Likert scale from not at all (0) to all the time (4), with a raw score calculated by a sum of the 4 items, ranging from 0 to 16. briefPCS is positively scored, where higher scores indicate greater levels of pain catastrophizing. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced pain catastrophizing).
Time frame: From baseline to end of treatment at Week 8
Population: All analyses will be performed by study arm using an Intent-to-Treat (ITT) population defined as all randomized participants. Participants who completed the briefPCS instrument at Week 8 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| painTRAINER (2D mHealth Intervention) | Change in 4-item Pain Catastrophizing Scale (briefPCS) | -1.8 units on a scale | Standard Deviation 3.5 |
| Skills-based VR (3D VR Intervention) | Change in 4-item Pain Catastrophizing Scale (briefPCS) | -1.7 units on a scale | Standard Deviation 3.2 |
Comparison: A two-sample t-test will be used to compare differences-in-differences between the arms.p-value: 0.831t-test, 2 sided
Secondary
Change in Patient-Reported Outcomes Measurement Information System Pain Interference 4a (PROMIS-PI) T-score
The Patient-Reported Outcomes Measurement Information System Pain Interference (PROMIS-PI) scale, version 4a, measures the consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Items are rated on a 5-point Likert scale from not at all (1) to very much (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-PI is positively scored, where higher scores indicate worse pain interference. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced PI).
Time frame: From baseline to end of treatment at Week 8
Population: All analyses were performed by study arm using an Intent-to-Treat (ITT) population, defined as all randomized participants. Participants who completed the PROMIS-PI instrument at Week 8 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| painTRAINER (2D mHealth Intervention) | Change in Patient-Reported Outcomes Measurement Information System Pain Interference 4a (PROMIS-PI) T-score | -4.5 T-score | Standard Deviation 6.3 |
| Skills-based VR (3D VR Intervention) | Change in Patient-Reported Outcomes Measurement Information System Pain Interference 4a (PROMIS-PI) T-score | -3.2 T-score | Standard Deviation 6 |
Comparison: A two-sample t-test will be used to compare differences-in-differences between the arms.p-value: 0.103t-test, 2 sided
Secondary
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety T-score
The Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale, version 4, assesses self-reported perceptions of fear, anxious misery (worry, dread), hyperarousal, and somatic symptoms related to arousal. Items are rated Items are rated on a 5-point Likert scale from never (1) to always (5), with a raw score calculated by a sum of the 4 items ranging from 4 to 20. Results are linked to a T-Score (healthmeasures.net) to standardize the results across a general population (a mean T-score of 50 and a standard deviation of 10). PROMIS-Anxiety is positively scored, where higher scores indicate worse anxiety. The difference from baseline is reported as Week 8 - Baseline, therefore a negative difference corresponds to improvement of symptoms (reduced anxiety).
Time frame: From baseline to end of treatment at Week 8
Population: All analyses were performed by study arm using an Intent-to-Treat (ITT) population, defined as all randomized participants. Participants who completed the PROMIS Anxiety instrument at Week 8 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| painTRAINER (2D mHealth Intervention) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety T-score | -0.3 T-score | Standard Deviation 7.6 |
| Skills-based VR (3D VR Intervention) | Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety T-score | -0.6 T-score | Standard Deviation 7.6 |
Comparison: A two-sample t-test will be used to compare differences-in-differences between the arms.p-value: 0.774t-test, 2 sided
Secondary
Change in Weekly Opioid Use (Use or No Use)
Opioid medications are commonly prescribed for pain analgesia. Participants self-reported their prescription and over-the-counter pain medications, daily for 7 days, at baseline (days -6 to 0) and during Week 8 of the study (days 50-56). The questionnaire contains lists of opioids and non-opioids. Responses were categorized based on whether or not an individual reported the use of an opioid medication on at least one of the daily surveys during baseline and during week 8; responses are reported as the proportion of individuals who reported the use of an opioid and who completed at least 4 daily questionnaires during the specified time period, divided by the total number of individuals who completed at least 4 daily questionnaires during the time interval, by arm. A smaller proportion at week 8 corresponds to a decrease in the frequency of opioid use in the observed sample.
Time frame: From baseline to end of treatment at Week 8
Population: Participants that responded to the medication use questionnaire in at least 4 out of 7 days administered during Baseline and during Week 8 were included in the each respective analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| painTRAINER (2D mHealth Intervention) | Change in Weekly Opioid Use (Use or No Use) | Baseline:Used Opioid in Past 7 Days | 67 Participants |
| painTRAINER (2D mHealth Intervention) | Change in Weekly Opioid Use (Use or No Use) | Week 8: Used Opioid in Past 7 Days | 44 Participants |
| Skills-based VR (3D VR Intervention) | Change in Weekly Opioid Use (Use or No Use) | Baseline:Used Opioid in Past 7 Days | 67 Participants |
| Skills-based VR (3D VR Intervention) | Change in Weekly Opioid Use (Use or No Use) | Week 8: Used Opioid in Past 7 Days | 45 Participants |
Comparison: The Cochran-Mantel-Haenszel (CMH) test was used to compare the association between time (baseline and week 8) and opioid use (yes or no) while stratifying for the treatment groups. The null hypothesis is that the common odds ratio of the association between time and response across the treatment groups is equal to 1, versus the alternative hypothesis that the common odds ratio is not equal to 1.p-value: 0.03195% CI: [1.03, 2.02]Cochran-Mantel-Haenszel